Lymphoma — Causes, Symptoms, Staging & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Lymphoma is a cancer of the lymphatic system arising from malignant proliferation of lymphocytes (B cells, T cells, or NK cells). It is classified into two major groups: Hodgkin lymphoma (HL), characterized by the pathognomonic Reed-Sternberg cell, and non-Hodgkin lymphoma (NHL), a heterogeneous group of over 60 distinct subtypes. HL accounts for approximately 10% of all lymphomas and typically occurs in young adults aged 15-35 and adults over 55. NHL affects over 80,000 Americans annually and is the sixth most common cancer worldwide. Most lymphomas originate in lymph nodes, but can arise in any lymphoid tissue — spleen, thymus, bone marrow, and extranodal sites including the gastrointestinal tract, skin, and central nervous system. Prognosis ranges from highly curable (HL, 5-year survival over 85%) to indolent but incurable (follicular lymphoma) to highly aggressive (Burkitt lymphoma requiring immediate treatment).

Most lymphomas arise from acquired somatic mutations in lymphocytes, often involving chromosome translocations that activate oncogenes or inactivate tumour suppressor genes. The t(14;18) BCL-2/IGH translocation is characteristic of follicular lymphoma; c-MYC translocations drive Burkitt lymphoma. Known risk factors for NHL include: immune suppression (HIV/AIDS, post-transplant immunosuppression — 100x increased NHL risk), autoimmune conditions (Sjogren's syndrome, rheumatoid arthritis, SLE), infections (Helicobacter pylori in gastric MALT lymphoma, EBV in Burkitt and post-transplant lymphoma, HTLV-1 in adult T-cell lymphoma), and exposure to pesticides, herbicides, and solvents. Hodgkin lymphoma is strongly associated with Epstein-Barr virus (EBV — detectable in Reed-Sternberg cells in 30-40% of cases). Genetic predisposition accounts for a minority of cases.

The most common presenting feature is painless, rubbery lymphadenopathy — enlarged lymph nodes that are non-tender, often in the cervical (neck), axillary (armpit), or inguinal (groin) regions. Hodgkin lymphoma classically involves contiguous nodal regions and may cause mediastinal mass causing cough, chest tightness, or superior vena cava syndrome (facial swelling, dyspnoea). Constitutional 'B symptoms' (occurring in 40-50% of HL and aggressive NHL) indicate advanced disease and include unexplained fever above 38°C, drenching night sweats, and unexplained weight loss over 10% of body weight in 6 months. Additional symptoms include splenomegaly causing early satiety, pruritus (itching — particularly in HL), and fatigue. Alcohol-induced lymph node pain (Pel-Ebstein phenomenon) is a rare but pathognomonic feature of HL. CNS lymphoma presents with headache, confusion, and focal neurological deficits.

Diagnosis requires excisional lymph node biopsy with histopathology, immunohistochemistry (CD20, CD3, CD30, CD15), and molecular studies. Fine needle aspiration is insufficient for lymphoma diagnosis. PET-CT scan is the gold standard for staging and response assessment — highly sensitive for identifying nodal and extranodal disease. Bone marrow biopsy assesses marrow involvement (required for accurate NHL staging). Ann Arbor staging (I-IV) classifies extent of disease. Complete blood count, LDH (elevated = poor prognosis), beta-2 microglobulin, albumin, renal and liver function, and infectious disease screening (HIV, hepatitis B — essential before rituximab therapy) complete the workup. International Prognostic Index (IPI) for NHL and International Prognostic Score (IPS) for HL stratify prognosis and guide treatment intensity. Genetic and molecular profiling (BCL-2, BCL-6, MYC rearrangements, cell of origin profiling in DLBCL) increasingly informs treatment selection.

Hodgkin lymphoma (early stage I-IIA): 2-4 cycles ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) + involved-field radiotherapy — cure rate above 90%. Advanced HL: 6 cycles ABVD or escalated BEACOPP; brentuximab vedotin (anti-CD30 antibody-drug conjugate) incorporated in frontline and relapsed HL. PD-1 inhibitors (nivolumab, pembrolizumab) highly effective in relapsed/refractory HL. Aggressive NHL (DLBCL): R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone) for 6 cycles — curative in 60-70%. Polatuzumab vedotin added to frontline for high-risk DLBCL. Indolent NHL (follicular lymphoma): watch-and-wait for asymptomatic low-burden disease; rituximab monotherapy or R-bendamustine for symptomatic disease — not curative but long progression-free survival. CAR-T cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, tisagenlecleucel) approved for relapsed/refractory DLBCL — produces durable remissions in 30-40% of heavily pretreated patients. Autologous stem cell transplantation for relapsed sensitive disease.

Aggressive lymphomas (DLBCL, Burkitt lymphoma) are rapidly fatal without treatment — median survival is weeks to months from progressive disease, organ failure, and bone marrow infiltration. Superior vena cava (SVC) syndrome from mediastinal lymphoma causes life-threatening venous obstruction with severe facial and arm swelling, and airway compromise requiring emergency radiotherapy or chemotherapy. Spinal cord compression from vertebral or epidural lymphoma causes paralysis if not treated within hours. CNS lymphoma (primary or secondary) causes rapid neurological decline — seizures, cognitive impairment, and herniation — with a dismal prognosis without treatment. Untreated advanced Hodgkin lymphoma, though more indolent, causes progressive systemic constitutional symptoms, lung involvement, bone marrow failure, and opportunistic infections from immune suppression. Even indolent follicular lymphoma eventually transforms to aggressive DLBCL (Richter's transformation variant) in approximately 2-3% of patients per year. Treatment-related long-term complications include secondary malignancies (therapy-related AML from alkylating agents, breast cancer from chest radiotherapy in Hodgkin survivors), and anthracycline-induced cardiomyopathy.

No universal screening exists for lymphoma. Risk reduction strategies: HIV prevention and effective antiretroviral therapy dramatically reduces AIDS-related lymphoma incidence. Eradication of H. pylori with triple antibiotic therapy achieves complete remission of gastric MALT lymphoma in over 75% of cases without chemotherapy — preventing early-stage disease from requiring systemic treatment. Minimise pesticide and organic solvent exposure in occupational settings. Post-transplant immunosuppression should be used at the lowest effective dose to limit PTLD (post-transplant lymphoproliferative disorder) risk. Immunosuppressed patients should undergo annual clinical assessment for lymphadenopathy. EBV-related lymphomas in immunocompromised patients may be prevented or identified early through regular monitoring. In those with a family history or high-risk autoimmune conditions, awareness of persistent lymphadenopathy prompts early evaluation.

Seek urgent medical assessment (within days) for any painless lymph node swelling lasting more than 2-3 weeks, particularly in the neck, armpit, or groin. See a doctor immediately for fever, night sweats, and weight loss occurring together — these B symptoms require prompt haematology evaluation. Emergency presentation is required for superior vena cava syndrome (rapidly worsening facial or arm swelling with dyspnoea), acute spinal cord compression, or severe shortness of breath from a large mediastinal mass. All suspected lymphoma cases should be referred to a haematologist for expert tissue biopsy and staging. Do not delay — some lymphomas (Burkitt, DLBCL) are rapidly fatal without treatment but highly curable with prompt diagnosis.